ABSTRACT
Immunotoxicity is defined as adverse effects on the functioning of the immune system that results from exposure to chemical substances. The present investigation was carried out to evaluate immunomodulating effect of Morus alba (500mg/kg B.w.) against immunotoxicity induced by sub-acute exposure of Fipronil (10mg/kg B.w.) in rats. Sub-acute immunotoxicity was conducted in adult male wistar rats. Rats were randomly divided into four groups (6 rats/group). Group I served as control in which corn oil (acting as a vehicle of Fipronil) was administered @10 ml/kg B.w. Group II served as Fipronil treated group @10 mg/kg B.w. In Group III Fipronil along with Morus alba fruits extract @ 300 mg/kg B.w. was administered and in Group IV Morus alba fruits extract @ 300 mg/kg B.w. was administered. Vehicle, Fipronil and Morus alba were administered daily to the rats by oral gavage for 28 days. The dose of fipronil was selected on the basis of LD50 in rats. TLC, DLC, serum total protein, albumin, globulin, A:G ratio, serum antibody titer/haemagglutination (HA) titer and delayed type hypersensitivity (DTH) response were estimated. Fipronil produced immunotoxicity in the form of alteration from normal values in these parameters. Morus alba was significantly effective in restoration of these parameters towards normal. The study suggested that Morus alba has immunomodulating potential against toxicity induced by fipronil in rats.
ABSTRACT
Viruses have been compatible with cells since the origin of life. The absolute dependence on cells leads to formation, development, distribution and evolution of viruses; the existence of viruses must have their long-term host for survival, spreading and extending. Like other species in nature, a group of viruses coexist with humans, which are called permanent resident virus in human being.The immune system of species has the function of anti-microbial invasion. The virus has a special coexistence mechanism with the long-term host. Because the immune system has no function to enter cells to recognize and remove viral nucleic acids, then invading viruses can be residual in cells, and as a recessive existence under the dynamic balance between residual viral replication and immune clearance pressure. This is the normal state of the virus with its long-term host coexisting harmoniously as stakeholders, and it also has been the normal state of all natural viruses after the immune system developed in host species, constituting the viral microecology of the host. The normal state viruses can undergo antigenic mutation to break through immune pressure and become abnormal, then viruses can proliferate again and spread to cause infection in host population, and would returned into normal state after a new immune protection to be established again. The primary infection of the normal state virus and the re-infection of the abnormal state virus can cause disease due to the immune toxicity induced by the immune response.The identification of permanent resident virus in human beings is of significant importance for studying the epidemiology, pathogenesis, clinical manifestations and outcomes of human viral diseases and epidemics, as well as prevention and treatment. Vaccine can successfully prevent the diseases caused by initial infection of normal state viruses. However, for the re-infection of abnormal state viruses, it is difficult to evaluate the preventive effect of vaccines because of the matching problem between previous vaccines and new antigens of abnormal state virus.
ABSTRACT
Environmental contaminants are one of the important causal factors for development of various human diseases. In particular, the perinatal period is highly vulnerable to environmental toxicants and resultant dysregulation of fetal development can cause detrimental health outcomes potentially affecting life-long health. Perfluoroalkyl compounds (PFCs), emerging environmental pollutants, are man-made organic molecules, which are widely used in diverse industries and consumer products. PFCs are non-degradable and bioaccumulate in the environment. Importantly, PFCs can be found in cord blood and breast milk as well as in the general population. Due to their physicochemical properties and potential toxicity, many studies have evaluated the health effects of PFCs. This review summarizes the epidemiological and experimental studies addressing the association of PFCs with neurotoxicity and immunotoxicity. While the relationships between PFC levels and changes in neural and immune health are not yet conclusive, accumulative studies provide evidence for positive associations between PFC levels and the incidence of attention deficit hyperactivity disorder and reduced immune response to vaccination both in children and adults. In conclusion, PFCs have the potential to affect human health linked with neurological disorders and immunosuppressive responses. However, our understanding of the molecular mechanism of the effects of PFCs on human health is still in its infancy. Therefore, along with efforts to develop methods to reduce exposure to PFCs, studies on the mode of action of these chemicals are required in the near future.
Subject(s)
Adult , Child , Humans , Attention Deficit Disorder with Hyperactivity , Environmental Pollutants , Fetal Blood , Fetal Development , Incidence , Milk, Human , Nervous System Diseases , VaccinationABSTRACT
Most monoclonal antibodies (mAbs) can induce immune responses.For immunomodulatory mAbs,immunotoxicity is the major toxicity.This article summarizes the characteristics of immunotoxicity,the factors associated with immunotoxicity,and the general considerations of nonclinical studies and evaluations.Before the clinical trials,comprehensive nonclinical studies on immunotoxicityshould be step by step conductedbased on mAbs' characteristics.If needed,some additional studies should be conducted.Attention should be paid to combination of in vivo and in vitro studies,combination of animal species and humanex vivo cells,and multiple approaches for studies.
ABSTRACT
The preclinical immunotoxicity evaluation of implantable medical devices was described.Firstly,the guidelines and regulations about the immunotoxicity evaluation of medical devices were summarized.These documents directed the immunotoxicity evaluation of implantable medical devices.Secondly,various aspects concerning the design of the immunotoxicity evaluation experiments were discussed here,including the hazardous effect of potential degradation products,the risk management of medical devices,the tests for interactions,the tests for in vitro cytotoxicity,the tests for local effects after implantation,the tests for irritation and delayed-type hypersensitivity,the tests for systemic toxicity.Thirdly,different types of immune responses with regard to immunotoxicity evaluation were listed and introduced here.In the end,the evaluation of implantable medical devices was expected to be more rigorous in the future.
ABSTRACT
The preclinical immunotoxicity evaluation of implantable medical devices was described.Firstly,the guidelines and regulations about the immunotoxicity evaluation of medical devices were summarized.These documents directed the immunotoxicity evaluation of implantable medical devices.Secondly,various aspects concerning the design of the immunotoxicity evaluation experiments were discussed here,including the hazardous effect of potential degradation products,the risk management of medical devices,the tests for interactions,the tests for in vitro cytotoxicity,the tests for local effects after implantation,the tests for irritation and delayed-type hypersensitivity,the tests for systemic toxicity.Thirdly,different types of immune responses with regard to immunotoxicity evaluation were listed and introduced here.In the end,the evaluation of implantable medical devices was expected to be more rigorous in the future.
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Objective To evaluate the immunity efficacy of human amniotic membranes on rats. Methods One hundred and fifty Wistar rats were randomly divided into five groups:biological amnion group,immunosuppression group,immunostimulation group, sham-operated group and blank control group. According to the study period,each group of thirty rats would be randomly divided into five experimental operation subgroups:the 1st week,the 2nd week,the 4th week,the 8th week group and the 12th week groups. The rats were implanted subcutaneously,then intramuscular injection of gentamicin sulfate for 3 days to resist the infection ,and the immune organ coefficient,and the killing abilities of NK cell ,IL-1β,IL-6 and TNF-αserum levels were detected according to the study period.Results At 1st ,2nd ,4th ,8th and 12th week after amniotic membrane implantation in rats,compared with the sham-operated and blank control groups,the biological amnion group had nonsignificant differences (P>0.05). At 1st week after amniotic membrane implantation in rats, immunosuppression group showed different levels of the immunosuppressive effect,such as the analysis of immune organ coefficient , which had significant differences compared with other groups (P<0.01). At 1st week after amniotic membrane implantation in rats,the imunostimulation group showed a certain degree of the immunostimulant effect,such as the killing abilities of NK cell,which had marked differences compared with other groups (P<0.05). Conclusion The amniotic membranes have satisfactory immune safety with implantation in rats and do not cause significant adverse immune reactions.
ABSTRACT
Objective: To evaluate the immunity efficacy of human amniotic membranes on rats. Methods: One hundred and fifty Wistar rats were randomly divided into five groups: biological amnion group, immunosuppression group, immunostimulation group, sham-operated group and blank control group. According to the study period, each group of thirty rats would be randomly divided into five experimental operation subgroups: the 1st week, the 2nd week, the 4th week, the 8th week group and the 12th week groups. The rats were implanted subcutaneously, then intramuscular injection of gentamicin sulfate for 3 days to resist the infection, and the immune organ coefficient, and the killing abilities of NK cell, IL-1β, IL-6 and TNF-αserum levels were detected according to the study period. Results: At 1st, 2nd, 4th, 8th and 12th week after amniotic membrane implantation in rats, compared with the sham-operated and blank control groups, the biological amnion group had nonsignificant differences(P>0.05). At 1st week after amniotic membrane implantation in rats, immunosuppression group showed different levels of the immunosuppressive effect, such as the analysis of immune organ coefficient, which had significant differences compared with other groups(P<0.01). At 1st week after amniotic membrane implantation in rats, the imunostimulation group showed a certain degree of the immunostimulant effect, such as the killing abilities of NK cell, which had marked differences compared with other groups(P<0.05). Conclusion: The amniotic membranes have satisfactory immune safety with implantation in rats and do not cause significant adverse immune reactions.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the immunotoxicity of acrylamide (ACR) in female BALB/c mice.</p><p><b>METHODS</b>A total of 200 female mice weighing 18-22 g were randomly divided into four clusters based on body weight, and each weight-based cluster included five groups (10 mice per group): negative control, positive control (cyclophosphamide), low, intermediate, and high dose ACR groups, and all the groups were administered ACR by gavage for 30 days. At the end of the study, the immunotoxicological effects of the ACR were evaluated through immunopathology, humoral immunity, cellular immunity, and non-specific immunity.</p><p><b>RESULTS</b>The terminal body weight, spleen and thymus weights, lymphocyte counts in the ACR-H group were decreased, pathological changes were observed in lymph glands, thymus and spleen. %T cells in blood lymphocytes were significantly increased in all ACR-treated groups, and a significant reduction of % natural killer(NK) cells and increase of %Th cells were observed in the ACR-H group. interleukin-6(IL-6), Concanavalin A(ConA)-induced splenocyte proliferation and serum half hemolysis value (HC50) were also significantly suppressed in the ACR-H group.</p><p><b>CONCLUSION</b>ACR elicited an inhibitory effect on cellular and humoral immunity of mice after 30 day feeding.</p>
Subject(s)
Animals , Female , Mice , Acrylamide , Toxicity , Body Weight , CD4-CD8 Ratio , Cytokines , Blood , Immunity, Cellular , Immunity, Humoral , Immunophenotyping , Immunotoxins , Toxicity , Mice, Inbred BALB C , Organ Size , Random Allocation , Spleen , Thymus Gland , Toxicity TestsABSTRACT
En las áreas costeras del norte de Chile es común encontrar en el agua para consumo humano niveles medios o altos de arsénico. La exposición al arsénico puede ir asociada a efectos agudos o crónicos. El objetivo de esta investigación fue determinar el daño histológico que provoca el trióxido de arsénico a nivel de los compartimentos del timo de ratas Sprague-Dawley. Se utilizaron 24 ratas de ambos sexos de 55 días de vida. Las ratas fueron pesadas y divididas en 3 grupos (4 hembras y 4 machos). A los grupos tratados se les aplicó 5 mg y 10 mg de As2O3 respectivamente, en dosis única diaria vía intraperitoneal por 15 días. Al grupo control se le aplicó agua destilada sin arsénico. Después del tratamiento los animales fueron sacrificados y retirado el timo de ellos, los cuales fueron lavados, pesados y seccionados en dos, luego se fijaron en formol tamponado al 10 por ciento. Mediante técnica histológica convencional se obtuvieron 4 muestras seriadas de cada timo, de 5 um de espesor y separadas por 100 um entre si, luego fueron teñidas con H-E. Se analizaron 30 campos (120 campos por órgano). Los resultados muestran que el As2O3 provoca la pérdida de celularidad en ambos compartimentos del timo, tanto en la corteza como en la médula, viéndose más afectado el compartimento medular (junto a la unión corticomedular). Se observó una reducción significativa del tamaño de la zona medular en ambos grupos tratados (5 y 10 mg de As2O3 respectivamente), siendo probablemente la disminución de este tejido el responsable de la atrofia del timo. Además se observó un aumento del tamaño de la corteza en las ratas hembras tratadas con 10 mg de As2O3. La unión corticomedular de las ratas tratadas se observó difusa o difícil de distinguir.
In coastal areas of northern Chile medium or high levels of arsenic are commonly found in drinking water. Arsenic exposure may be associated with acute or chronic effects. The objective of this investigation was to determine the histological damage caused by arsenic trioxide level of the compartments of the thymus of Sprague-Dawley rats. We used 24 rats of both sexes of 55 days of life. The rats were weighed and divided into 3 groups (4 females and 4 males). In the treated groups were administered 5 mg and 10 mg of As2O3 respectively, in a single daily dose for 15 days intraperitoneally. The control group was administered distilled water without arsenic. After treatment the animals were sacrificed and the thymus removed, washed, weighed and divided into two, then fixed in 10 percent buffered formalin. By conventional histology samples were obtained serially every 4 thymus, 5 microns thick and separated by 100 microns each, then were stained with HE. We analyzed 30 fields (120 fields per organ). The results showed that As2O3 causes loss of cellularity in both compartments of the thymus, both in the cortex and in the bone, medullary compartment was more affected (near the corticomedullary junction). There was a significant reduction in the size of the medulla in both groups (5 and 10 mg As2O3 respectively), probably the decrease of the tissue responsible for thymic atrophy. We observed an increase in the size of the cortex in female rats treated with 10 mg of As2O3. The corticomedullary junction of the treated rats showed diffuse or difficult to distinguish.
Subject(s)
Animals , Female , Rats , Arsenic/toxicity , Thymus Gland , Thymus Gland/pathology , Atrophy , Arsenic/administration & dosage , Arsenic Poisoning/pathology , Oxides/toxicity , Body Weight , Rats, Sprague-DawleyABSTRACT
Cyclosporine A (CsA) is widely used as an immunosuppressant for the treatment of autoimmune diseases and immune regulation in transplant patients. Due to its wide applicability, studies of unwanted side effects of CsA are imperative. It has been found that not all patients treated with CsA display the same types/patterns of adverse effects. To ascertain the bases for these differential responses, potential differing effects of CsA on B-lymphocytes were analyzed. This entailed an assessment of changes in CsA viability and mitotic activity within splenocyte populations from BALB/c and ICR mice. These particular strains were examined because: (1) in each of them, previously have been shown that differed in the respond to biological response modifiers, such as bacterial agents, and/or immunogens; (2) our own earlier studies showing strain-associated differences in ex vivo splenocyte/lymphocyte responses to other drug; and, (3) a potential immunomodulatory effect of any agent should be studied in at least two different strains during a broad toxicological evaluation. Splenocytes from each strain were treated with 200 μg/mL CsA, and CD4+, CD8+, and CD19+ cell viabilities were monitored at various time points during the exposure period. In general, there appeared to be a trend toward greater decreases in viability among BALB/c B-lymphocytes than their ICR counterparts as incubation progressed. Differences related with T-lymphocyte sensitivity to drug associated to strains was not observed, because it was uniformly lethal throughout. With regard to mitotic activity, cells from ICR mice were more susceptible to inhibition of spontaneous cell division at low concentrations of CsA (relative to the rates of blastogenesis by BALB/c counterparts). At higher concentrations of the drug however, there were no differences in the sensitivity of each strain. This work provides new insight into the mechanism of action of CsA and illustrates the need for at least two different strains of mice/rodents for the evaluation of the overall toxicological potential of any test agent.
Ciclosporina A (CsA) é amplamente usada como imunossupressor para o tratamento de doenças autoimunes e regulação imune nos pacientes transplantados. Devido à alta aplicabilidade, são imperativos os estudos sobre seus efeitos colaterais indesejáveis. Descobriu-se que nem todos os pacientes tratados com CsA apresentam os mesmos tipos/padrões de efeitos adversos. Para averiguar as bases dessas respostas diferentes, analisaram-se efeitos potenciais diferentes da CsA nos linfócitos B. Isto envolveu a avaliação de alterações na viabilidade da CsA e da atividade mitótica dentro das populações de esplenócitos de camundongos BALB/c e ICR. Essas espécies, em particular, foram examinadas porque: (1) cada uma delas mostrou, previamente, respostas diferentes a modificadores de respostas biológicas, tais como agentes bacterianos e/ou imunogênicos; (2) nossos estudos anteriores mostraram diferenças associadas às espécies em respostas ex vivo de esplenócitos/linfócitos a outro fármaco e (3) qualquer efeito imunomodulatório potencial de um agente em teste deveria ser estudado, no mínimo, em duas espécies diferentes durante a avaliação toxicológica ampla. Esplenócitos de cada espécie foram tratados com 200 μg/mL de CSA e a viabilidade das células CD4+, CD8+ e CD19+ foi monitorada em vários tempos durante o período de exposição. No geral, parece haver uma tendência em relação a aumentos maiores na viabilidade entre os linfócitos B de BALB/c do que no de ICR, à medida que a incubação progride. Não se observou diferenças na sensibilidade do linfócito T, uma vez que o fármaco foi uniformemente letal. Com relação à atividade mitótica, as células de camundongos ICR se mostraram mais suscetíveis à inibição da divisão celular espontânea em baixas concentrações de CsA (relativamente às taxas de blastogênese de BALB/c). Em concentrações maiores do fármaco, entretanto, não houve diferenças na sensibilidade em cada uma das espécies. Este trabalho propicia nova visão do mecanismo de ação de CsA e ilustra a necessidade de, pelo menos, duas espécies diferentes de camundongos/roedores para a avaliação da toxicidade potencial de qualquer agente em teste.
Subject(s)
Animals , Female , Adult , Mice , Spleen/cytology , Spleen , Cyclosporine/immunology , Immunologic Factors/analysis , Immunotoxins/analysis , Immunotoxins/adverse effects , Mice, Inbred BALB C , Mice, Inbred ICR , Lymphocyte Activation , B-LymphocytesABSTRACT
The effect of N-acetylcysteine, a thiolic antioxidant, on attenuation of phosphamidon-induced oxidative stress and immune dysfunction was evaluated in adult male Wistar rats weighing 200-250 g. Rats were divided into four groups, 8 animals/group, and treated with phosphamidon, N-acetylcysteine or the combination of both for 28 days. Oral administration of phosphamidon (1.74 mg/kg), an organophosphate insecticide, increased serum malondialdehyde (3.83 ± 0.18 vs 2.91 ± 0.24 nmol/mL; P < 0.05) and decreased erythrocyte superoxide dismutase (567.8 ± 24.36 vs 749.16 ± 102.61 U/gHb; P < 0.05), catalase activity (1.86 ± 0.18 vs 2.43 ± 0.08 U/gHb; P < 0.05) and whole blood glutathione levels (1.25 ± 0.21 vs 2.28 ± 0.08 mg/gHb; P < 0.05) showing phosphamidon-induced oxidative stress. Phosphamidon exposure markedly suppressed humoral immune response as assessed by antibody titer to ovalbumin (4.71 ± 0.51 vs 8.00 ± 0.12 -log2; P < 0.05), and cell-mediated immune response as assessed by leukocyte migration inhibition (25.24 ± 1.04 vs 70.8 ± 1.09%; P < 0.05) and macrophage migration inhibition (20.38 ± 0.99 vs 67.16 ± 5.30%; P < 0.05) response. Phosphamidon exposure decreased IFN-у levels (40.7 ± 3.21 vs 55.84 ± 3.02 pg/mL; P < 0.05) suggesting a profound effect of phosphamidon on cell-mediated immune response. A phosphamidon-induced increase in TNF-α level (64.19 ± 6.0 vs 23.16 ± 4.0 pg/mL; P < 0.05) suggests a contributory role of immunocytes in oxidative stress. Co-administration of N-acetylcysteine (3.5 mmol/kg, orally) with phosphamidon attenuated the adverse effects of phosphamidon. These findings suggest that oral N-acetylcysteine treatment exerts protective effect and attenuates free radical injury and immune dysfunction caused by subchronic phosphamidon exposure.
Subject(s)
Animals , Male , Rats , Acetylcysteine/pharmacology , Antibody Formation/drug effects , Free Radical Scavengers/pharmacology , Insecticides/toxicity , Oxidative Stress/drug effects , Phosphamidon/toxicity , Antibody Formation/immunology , Cell Migration Assays, Leukocyte , Glutathione/blood , Immunity, Cellular/drug effects , Interferon-gamma/metabolism , Malondialdehyde/blood , Ovalbumin/immunology , Rats, Wistar , Superoxide Dismutase/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Acephate (Ace) is an organophosphate foliar spray insecticide of moderate persistence with residual systemic activity of about 10–15 days. This study was designed to evaluate the immunotoxic effect of oral subacute acephate exposure in 125-day old WLH Cockerel chicks for 28 days. The experimental birds were randomly divided into five groups (C1, C2, T1, T2 and T3), each comprising 25 birds. The birds of group C1 were given no treatment and served as control. Group C2 was administered groundnut oil (1ml/kg) and served as control (vehicle). Group T1 was given ALD50/40 (21.3 mg/kg), and Group T2 was put on ALD50/30 (28.4 mg/kg), while group T3 received ALD50/20 (42.6 mg/kg) of acephate suspended in groundnut oil. Experimental birds of all groups were vaccinated with New Castle disease vaccine at day 7. Blood was collected at two-week intervals for evaluation of humoral immune response. Parameters such as TLC, TP, antibody titre against ND vaccine, DNCB dye test, and histopathology of immune organs were studied to evaluate immunotoxicity. The results were statistically compared (p<0.05) with the control. Acephate produced decreased humoral immune response in terms of New Castle disease vaccine antibody titre, total protein, serum globulin, and serum albumin. Cell mediated immune response was checked with 1-chloro 2, 4 dinitrobenzene dye dermal sensitization test, and it did not reveal any significant differences. Lymphoid organs such as thymus, spleen, bursa, and liver were weighed during necropsy for calculation of organ weight: body weight ratio. After 28 days of acephate exposure, organ:body weight ratios of immune organs were significantly reduced except liver:body weight ratio on 14 days of exposure, which was increased in all treatment groups as compared to control groups. Histopathologically, bursa and spleen showed mild depletion of lymphocytes. To further identify the specific type of cell death as apoptotic or necrotic, DNA ladder assay was performed. DNA fragmentation assay detected ladder pattern (180bp) in DNA from hepatocytes and splenocytes of acephate-treated birds. It is concluded that acephate is immunotoxic, and exerts its immunotoxicity through induction of apoptosis and alteration of immunological parameters.
ABSTRACT
Beryllium induces non-caseating granulomatous inflammation in humans exposed to the metal dust or fumes in both occupational and non-occupational settings. The resulting condition, chronic beryllium disease (CBD), affects principally the lungs, lymphatics, and skin and continues to plague modern industry. Beryllium exerts several important immunotoxic effects, including induction of a beryllium-antigen specific adaptive immune response and the triggering of inflammatory and innate immune responses. Genetic susceptibility plays a role in CBD adaptive immune responses, mainly mediated through single nucleotide polymorphisms in HLA-DP and, to a lesser extent, HLA-DR. The adaptive response is characterized by influx and proliferation of CD4+ central and effector memory T cells expressing Th1 cytokines. Insights into the immunopathogenesis of CBD have implications for the understanding of other immune-mediated granulomatous disorders and for metal antigen behavior.
ABSTRACT
Beryllium induces non-caseating granulomatous inflammation in humans exposed to the metal dust or fumes in both occupational and non-occupational settings. The resulting condition, chronic beryllium disease (CBD), affects principally the lungs, lymphatics, and skin and continues to plague modern industry. Beryllium exerts several important immunotoxic effects, including induction of a beryllium-antigen specific adaptive immune response and the triggering of inflammatory and innate immune responses. Genetic susceptibility plays a role in CBD adaptive immune responses, mainly mediated through single nucleotide polymorphisms in HLA-DP and, to a lesser extent, HLA-DR. The adaptive response is characterized by influx and proliferation of CD4+ central and effector memory T cells expressing Th1 cytokines. Insights into the immunopathogenesis of CBD have implications for the understanding of other immune-mediated granulomatous disorders and for metal antigen behavior.
Subject(s)
Immunity , Common Bile Duct , OccupationsABSTRACT
<p><b>OBJECTIVE</b>Tributyltin (TBT) compounds have been widely used as antifouling agents for shipbottom paint. The immune system is a target of TBT intoxication. We evaluated the effects of TBT chloride in macrophages, which have critical roles in the immune system, using a murine macrophage lineage cell line, J774.1,in vitro.</p><p><b>METHODS</b>We examined tumor necrosis factor α (TNFα), interleukin-1β (IL-1β) andc-jun mRNA expression in J774.1 cells. The effects of TBT on the apoptosis of J774.1 cells were examined by determining the percentage of TUNEL-positive cells and caspase-3 activity.</p><p><b>RESULTS</b>The mean values of the viabilities of J774.1 cells exposed to TBT decreased dose-dependently. The relative mRNA expression of TNFα increased dose-dependently, however, that of IL-1β was not significantly different among the groups. The mean percentage of TUNEL-positive cells increased dose-dependently. Increases in the caspase-3 activities of J774.1 cells were observed in the groups exposed to higher concentrations of TBT. The mean value of relative mRNA expression of c-Jun transcription factor increased dose-dependently.</p><p><b>CONCLUSIONS</b>The increases in the percentage of TUNEL-positive cells and in caspase-3 activity suggested that exposure to TBT induces apoptosis of J774.1 cells. The increases in the mRNA expression of TNFα andc-jun by TBT may be related to apoptosis in macrophages.</p>
ABSTRACT
Objective: Tributyltin (TBT) compounds have been widely used as antifouling agents for ship-bottom paint. The immune system is a target of TBT intoxication. We evaluated the effects of TBT chloride in macrophages, which have critical roles in the immune system, using a murine macrophage lineage cell line, J774.1, in vitro. Methods: We examined tumor necrosis factor α (TNF α), interleukin-1β (IL-1β) and c-jun mRNA expression in J774.1 cells. The effects of TBT on the apoptosis of J774.1 cells were examined by determining the percentage of TUNEL-positive cells and caspase-3 activity. Results: The mean values of the viabilities of J774.1 cells exposed to TBT decreased dose-dependently. The relative mRNA expression of TNFα increased dose-dependently, however, that of IL-1β was not significantly different among the groups. The mean percentage of TUNEL-positive cells increased dose-dependently. Increases in the caspase-3 activities of J774.1 cells were observed in the groups exposed to higher concentrations of TBT. The mean value of relative mRNA expression of c-Jun transcription factor increased dose-dependently. Conclusions: The increases in the percentage of TUNEL-positive cells and in caspase-3 activity suggested that exposure to TBT induces apoptosis of J774.1 cells. The increases in the mRNA expression of TNFα and c-jun by TBT may be related to apoptosis in macrophages.
Subject(s)
Tumor Necrosis Factor-alpha , RNA, Messenger , Apoptosis , In Situ Nick-End LabelingABSTRACT
Organophosphorus pesticides(OP) are used as insecticides in agriculture throughout the world.The main toxicity of OP is neurotoxicity,which is caused by the inhibition of acetylcholinesterase.OPs also affect the immune response and suppress antibody production,T cell proliferation and the activity of natural killer(NK) cells and cytotoxic T lymphocytes(CTL).However,there have been few studies on the mechanism of OP-induced immunotoxicity,especially the mechanism of OP-induced inhibition of the cytolytic activity of killer cells.This study updates the mechanisms of pesticide-induced immunotoxicity,including its direct and indirect effects on the immune system.
ABSTRACT
<p><b>OBJECTIVES</b>To clarify whether di (2-ethylhexyl) phthalate (DEHP) has immunotoxic effects on both the expression of surface molecules (CD3, CD4, CD8 and CD28) on T cells of the thymus and spleen in male C57BL/6 mice.</p><p><b>METHODS</b>Animals were orally administered a 0.1% or 0.2% DEHP-containing diet for 10 or 20 days. Dietary corn oil was used as the vehicle for DEHP in preparing the diet.</p><p><b>RESULTS</b>Significant hepatic hypertrophy was clearly observed in the DEHP-exposed groups, while no atrophy was seen in the thymus or spleen in any treatment groups. In the thymus and spleen, no variation in the proportions of both T cells expressing CD3, CD4 and CD8 was shown with cytometry analysis. The surface expression of CD3, CD4, CD8 and CD28 on both T cells was also invariable in all analyzed stages of thymic differentiation and in the spleen. No effect of DEHP on mitogenesis was shown in the splenic T cells with anin vitro [(3)H]-thymidine-incorporation technique.</p><p><b>CONCLUSIONS</b>DEHP is probably not an immunosuppressor, particularly for T cells.</p>
ABSTRACT
Objectives: To clarify whether di (2-ethylhexyl) phthalate (DEHP) has immunotoxic effects on both the expression of surface molecules (CD3, CD4, CD8 and CD28) on T cells of the thymus and spleen in male C57BL/6 mice. Methods: Animals were orally administered a 0.1% or 0.2% DEHP-containing diet for 10 or 20 days. Dietary corn oil was used as the vehicle for DEHP in preparing the diet. Results: Significant hepatic hypertrophy was clearly observed in the DEHP-exposed groups, while no atrophy was seen in the thymus or spleen in any treatment groups. In the thymus and spleen, no variation in the proportions of both T cells expressing CD3, CD4 and CD8 was shown with cytometry analysis. The surface expression of CD3, CD4, CD8 and CD28 on both T cells was also invariable in all analyzed stages of thymic differentiation and in the spleen. No effect of DEHP on mitogenesis was shown in the splenic T cells with an in vitro [3H]-thymidine-incorporation technique. Conclusions: DEHP is probably not an immunosuppressor, particularly for T cells.